{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T16:46:12Z","timestamp":1793724372648,"version":"4.6.1"},"reference-count":43,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Pathological pregnancy is associated with various complications that may affect the health of both the mother and her offspring. In recent years, lipid metabolites such as hydroxyeicosatetraenoic (HETE) fatty acids and hydroxyoctadecadienoic (HODE) fatty acids have gained increasing interest as potential biomarkers of pathological processes in pregnancy. The aims of the present study were to investigate changes in HETE and HODE levels during pathological pregnancy and to assess their potential role in the development and monitoring of pregnancy complications. Attempts were made to determine associations in cross-sectional studies and relationships in longitudinal ones. Methods: In this study, a liquid chromatograph (HPLC) was used to separate the eicosanoids. The study group consisted of 72 Caucasian women, divided into a control group (n = 51) and a group with non-physiological pregnancy (n = 21). Results: The study results show that the levels of the tested metabolites of the cyclooxygenase (COX) and lipoxygenase (LOX) pathways increased as pregnancy progressed. Women with non-physiological courses of pregnancy who developed gestational diabetes and\/or preeclampsia were characterized by dysregulation of the inflammatory signaling processes involving eicosanoids. Conclusions: Carbohydrate abnormalities during pregnancy were mainly associated with increased synthesis of 5-oxoETE and the use of 5-HETE in the control group but were not visible in the diabetic group. HODE acids probably do not play a significant role in pathological pregnancy. The relatively small size of the pathological group and the wide range of gestational age mean that the tests should be standardized and carried out on a larger scale.<\/jats:p>","DOI":"10.3390\/nu17193170","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T08:22:08Z","timestamp":1759911728000},"page":"3170","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Metabolites of the Arachidonic Acid Lipoxygenase Pathway May Be Targets for Intervention and Diagnostic Markers for Metabolic Disorders in Pregnancy\u2014A Pilot Study"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9808-0624","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Szczuko","sequence":"first","affiliation":[{"name":"Department of Bromatology and Nutritional Diagnostics, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justyna","family":"Maj","sequence":"additional","affiliation":[{"name":"Department of Bromatology and Nutritional Diagnostics, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4835-8517","authenticated-orcid":false,"given":"Kamila","family":"Pokorska-Niewiada","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Dairy Technology and Food Storage, West Pomeranian University of Technology in Szczecin, 71-459 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6401-627X","authenticated-orcid":false,"given":"Edyta","family":"Zagrodnik","sequence":"additional","affiliation":[{"name":"Clinical Department of Anesthesiology and Intensive Care of Adults and Children, Pomeranian Medical University in Szczecin, 72-010 Police, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7729-0670","authenticated-orcid":false,"given":"Maciej","family":"Zi\u0119tek","sequence":"additional","affiliation":[{"name":"Department of Perinatology, Obstetrics and Gynecology, Pomeranian Medical University in Szczecin, 72-010 Police, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"280.e1","DOI":"10.1016\/j.ajog.2021.03.048","article-title":"Metabolic syndrome in obesity: Treatment success and adverse pregnancy outcomes with ovulation induction in polycystic ovary syndrome. National Institute of Child Health and Human Development Reproductive Medicine Network","volume":"225","author":"Arya","year":"2021","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Jouanne, M.S., Oddoux, S., No\u00ebl, A., and Voisin-Chiret, A.S. (2021). Nutrient Requirements during Pregnancy and Lactation. Nutrients, 13.","DOI":"10.3390\/nu13020692"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.srhc.2016.01.005","article-title":"Naegele\u2019s rule revisited","volume":"8","author":"Loytved","year":"2016","journal-title":"Sex. Reprod. Healthc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.ejogrb.2018.02.026","article-title":"Duration of spontaneous labour in \u2018low-risk\u2019 women with \u2018normal\u2019 perinatal outcomes: A systematic review","volume":"223","author":"Abalos","year":"2018","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.tem.2018.09.004","article-title":"Gestational Diabetes Mellitus: Mechanisms, Treatment, and Complications","volume":"29","author":"Johns","year":"2018","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.spsy.2022.11.005","article-title":"Complementarity of body\/psyche care in case of postpartum depression","volume":"43","author":"Agbokou","year":"2022","journal-title":"Soins Psychiatr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1530\/REP-09-0247","article-title":"Inflammatory pathways in female reproductive health and disease","volume":"138","author":"Jabbour","year":"2009","journal-title":"Reproduction"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"103177","DOI":"10.1016\/j.jri.2020.103177","article-title":"Inflammation with the participation of arachidonic (AA) and linoleic acid (LA) derivatives (HETEs and HODEs) is necessary in the course of a normal reproductive cycle and pregnancy","volume":"141","author":"Kikut","year":"2020","journal-title":"J. Reprod. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Szczuko, M., Kikut, J., Komorniak, N., Bilicki, J., Celewicz, Z., and Zi\u0119tek, M. (2020). The Role of Arachidonic and Linoleic Acid Derivatives in Pathological Pregnancies and the Human Reproduction Process. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249628"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e218401","DOI":"10.1001\/jamanetworkopen.2021.8401","article-title":"Preeclampsia Prevalence. Risk Factors. and Pregnancy Outcomes in Sweden and China","volume":"4","author":"Yang","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e21","DOI":"10.1161\/HYP.0000000000000208","article-title":"Hypertension in Pregnancy: Diagnosis, Blood Pressure Goals, and Pharmacotherapy: A Scientific Statement From the American Heart Association","volume":"79","author":"Garovic","year":"2022","journal-title":"Hypertension"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"(2020). Management of Diabetes in Pregnancy: Standards of Medical Care in Diabetes-2020. American Diabetes Association. Diabetes Care., 43, S183\u2013S192.","DOI":"10.2337\/dc20-S014"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1210\/endrev\/bnac003","article-title":"A Clinical Update on Gestational Diabetes Mellitus","volume":"43","author":"Sweeting","year":"2022","journal-title":"Endocr. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.jogc.2016.04.002","article-title":"Diabetes in Pregnancy","volume":"38","author":"Berger","year":"2016","journal-title":"J. Obstet. Gynaecol. Can."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"He, J., Song, J., Zou, Z., Fan, X., Tian, R., Xu, J., Yan, Y., Bai, J., Chen, Z., and Liu, Y. (2022). Association between neonatal hyperbilirubinemia and hypoglycemia in Chinese women with diabetes in pregnancy and influence factors. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-21114-6"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41392-020-00443-w","article-title":"Metabolism pathways of arachidonic acids: Mechanisms and potential therapeutic targets","volume":"6","author":"Wang","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Devarshi, P.P., Grant, R.W., Ikonte, C.J., and Hazels Mitmesser, S. (2019). Maternal Omega-3 Nutrition, Placental Transfer and Fetal Brain Development in Gestational Diabetes and Preeclampsia. Nutrients, 11.","DOI":"10.3390\/nu11051107"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Martinat, M., Rossitto, M., Di Miceli, M., and Lay\u00e9, S. (2021). Perinatal Dietary Polyunsaturated Fatty Acids in Brain Development, Role in Neurodevelopmental Disorders. Nutrients, 13.","DOI":"10.3390\/nu13041185"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Urech, C., Eussen, S.R.B.M., Alder, J., Stahl, B., Boehm, G., Bitzer, J., Bartke, N., and Hoesli, I. (2020). Levels of n-3 and n-6 Fatty Acids in Maternal Erythrocytes during Pregnancy and in Human Milk and Its Association with Perinatal Mental Health. Nutrients, 12.","DOI":"10.3390\/nu12092773"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1007\/s11745-014-3954-z","article-title":"Hydroxyoctadecadienoic acids regulate apoptosis in human THP-1 cells in a PPAR\u03b3-dependent manner","volume":"49","author":"Vangaveti","year":"2014","journal-title":"Lipids"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5489523","DOI":"10.1155\/2017\/5489523","article-title":"Significant Improvement Selected Mediators of Inflammation in Phenotypes of Women with PCOS after Reduction and Low GI Diet","volume":"2017","author":"Szczuko","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Memon, A., and Lee, W.K. (2018). KLF10 as a Tumor Suppressor Gene and Its TGF-\u03b2 Signaling. Cancers, 10.","DOI":"10.3390\/cancers10060161"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.prostaglandins.2013.07.002","article-title":"Effect of human 15-lipoxygenase-1 metabolites on vascular function in mouse mesenteric arteries and hearts","volume":"106","author":"Kriska","year":"2013","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Lubrano, V., Ndreu, R., and Balzan, S. (2023). Classes of Lipid Mediators and Their Effects on Vascular Inflammation in Atherosclerosis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021637"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Welch, B.M., Keil, A.P., van \u2018t Erve, T.J., Deterding, L.J., Williams, J.G., Lih, F.B., Cantonwine, D.E., McElrath, T.F., and Ferguson, K.K. (2020). Longitudinal profiles of plasma eicosanoids during pregnancy and size for gestational age at delivery: A nested case-control study. PLoS Med., 17.","DOI":"10.1371\/journal.pmed.1003271"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Szczuko, M., Kotl\u0119ga, D., Palma, J., Zembro\u0144-\u0141acny, A., Tylutka, A., Go\u0142\u0105b-Janowska, M., and Drozd, A. (2020). Lipoxins, RevD1 and 9, 13 HODE as the most important derivatives after an early incident of ischemic stroke. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-69831-0"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Walsh, S.W., and Strauss, J.F. (2021). The Road to Low-Dose Aspirin Therapy for the Prevention of Preeclampsia Began with the Placenta. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136985"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1097\/HJH.0b013e32833e86aa","article-title":"Measurement of vasoactive metabolites (hydroxyeicosatetraenoic and epoxyeicosatrienoic acids) in uterine tissues of normal and compromised human pregnancy","volume":"28","author":"Pearson","year":"2010","journal-title":"J. Hypertens."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"118590","DOI":"10.1016\/j.lfs.2020.118590","article-title":"Changes in erythrocyte membrane epoxyeicosatrienoic, dihydroxyeicosatrienoic, and hydroxyeicosatetraenoic acids during pregnancy","volume":"264","author":"Somani","year":"2021","journal-title":"Life Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2236","DOI":"10.1097\/HJH.0000000000003253","article-title":"Mediators of inflammation resolution and vasoactive eicosanoids in gestational diabetes and preeclampsia","volume":"40","author":"Barden","year":"2022","journal-title":"J. Hypertens."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"R166","DOI":"10.1186\/cc11518","article-title":"Eliminating or blocking 12\/15-lipoxygenase reduces neutrophil recruitment in mouse models of acute lung injury","volume":"16","author":"Rossaint","year":"2012","journal-title":"Crit. Care"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"106648","DOI":"10.1016\/j.prostaglandins.2022.106648","article-title":"Functional and pathological role of 15-Lipoxygenase and its metabolites in pregnancy and pregnancy-associated complications","volume":"161","author":"Eghtedari","year":"2022","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.bbalip.2014.10.008","article-title":"Biosynthesis, biological effects and receptors of hydroxyeicosatetraenoic acids (HETEs) and oxoeicosatetraenoic acids (oxo-ETEs) derived from arachidonic acid","volume":"1851","author":"Powell","year":"2015","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"100294","DOI":"10.1016\/j.jlr.2022.100294","article-title":"Identification of a Feed-Forward Loop Between 15(S)-HETE and PGE2 in Human Amnion at Parturition","volume":"63","author":"Zhang","year":"2022","journal-title":"J. Lipid Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.plefa.2011.10.006","article-title":"Preeclampsia activates 15-lipoxygenase and its metabolite 15-hydroxyeicosatetraenoic acid enhances constriction in umbilical arteries","volume":"86","author":"Wang","year":"2012","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.placenta.2020.10.007","article-title":"Serum leukotriene B4 and hydroxyeicosatetraenoic acid in the prediction of pre-eclampsia","volume":"103","author":"Santos","year":"2021","journal-title":"Placenta"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.ijgo.2015.10.024","article-title":"Association between the maternal serum levels of 19 eicosanoids and pre-eclampsia","volume":"133","author":"Long","year":"2016","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Yuan, D., Ran, Y., Liu, Q., Zhang, Y., Li, H., Li, P., and Zhu, D. (2014). Enhancement of the HIF-1\u03b1\/15-LO\/15-HETE axis promotes hypoxia-induced endothelial proliferation in preeclamptic pregnancy. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0096510"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1095\/biolreprod.107.064717","article-title":"Effect of the Interaction Between Lipoxygenase Pathway and Progesterone on the Regulation of Hydroxysteroid 11-Beta Dehydrogenase 2 in Cultured Human Term Placental Trophoblasts1","volume":"78","author":"Sato","year":"2008","journal-title":"Biol. Reprod."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1111\/j.1476-5381.2009.00386.x","article-title":"Lipoxins: Resolutionary road","volume":"158","author":"Maderna","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"102041","DOI":"10.1016\/j.plefa.2019.102041","article-title":"Plasma oxylipins and unesterified precursor fatty acids are altered by DHA supplementation in pregnancy: Can they help predict risk of preterm birth?","volume":"153","author":"Ramsden","year":"2020","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"E647","DOI":"10.1152\/ajpendo.00227.2009","article-title":"Detection of EETs and HETE-generating cytochrome P-450 enzymes and the effects of their metabolites on myometrial and vascular function","volume":"297","author":"Pearson","year":"2009","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.prostaglandins.2012.12.002","article-title":"Elevated level of pro-inflammatory eicosanoids and EPC dysfunction in diabetic patients with cardiac ischemia","volume":"100\u2013101","author":"Issan","year":"2013","journal-title":"Prostaglandins Other Lipid Mediat."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/19\/3170\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:50:17Z","timestamp":1760035817000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/19\/3170"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,8]]},"references-count":43,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["nu17193170"],"URL":"https:\/\/doi.org\/10.3390\/nu17193170","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,8]]}}}